Chants of "Let's go, Andy!" rang out between points during the last service game of his career, and again before the start of what would wind up as the last return game.

Always a fan favorite at the U.S. Open, and the 2003 champion, Andy Roddick headed into retirement with a 6-7 (1), 7-6 (4), 6-2, 6-4 loss to Juan Martin del Potro of Argentina in the fourth round at Flushing Meadows on Wednesday.

It was an emotional farewell for Roddick, who sat in his changeover chair, covering his face with a white towel, after sailing a running forehand long on the last point. He choked up during an on-court speech at Arthur Ashe Stadium, telling the crowd, "Oh, wow. For the first time in my career, I'm not sure what to say."

"Since I was a kid, I've been coming to this tournament. I felt lucky just to sit where all of you are sitting today, to watch this game, to see the champions that have come and gone," Roddick told the fans. "I've loved every minute of it."

The American surprisingly announced last Thursday, his 30th birthday, that the U.S. Open would be his final tournament. That impromptu news conference came a day before Roddick's second-round match, and he wound up winning that one, and a third-rounder, too, riding a wave of support in the stands.

But those two opponents were ranked 43rd and 59th, and the seventh-seeded del Potro, the 2009 U.S. Open champion, provided a far more daunting challenge -- especially once he lifted his energy level and got his big, flat forehand cranked up.

The match was suspended because of rain Tuesday night after Roddick took the first point of the opening-set tiebreaker, and they resumed more than 18 hours later in front of thousands of empty blue seats. It took Roddick only four minutes to close that set, fresh and strong as can be, while del Potro was rather sluggish.

The key, probably, was the second set. Neither man faced so much as a single break point, and this time it was del Potro's turn to dominate the tiebreaker. Gaining more traction on his opponent's once-all-powerful serve, del Potro whipped a cross-court forehand return right at Roddick's feet on set point.

Del Potro's momentum swing continued when he broke to begin the third set. He hit a drop shot that Roddick chased, grunting loudly, and eventually del Potro deposited a passing winner that left Roddick hanging his head.

Del Potro broke again for a 3-0 edge in that set, producing a drop shot winner that Roddick didn't even chase. As he walked to the sideline for the changeover, Roddick grimaced and flexed his right shoulder -- the one that hit a then-record 155 mph serve years ago but now aches. He jokingly referred to it as "Hamburger helper" after his previous match.

Up 1-0 in the fourth, Roddick got a chance to make one last stand and postpone retirement for at least a set, if not another match, when del Potro double-faulted to hand over a break point. But Roddick sailed a backhand long, then dropped his racket at his feet and leans forward with hands on head, the very picture of exasperation.

When Roddick double-faulted, then missed a forehand, to fall behind 3-2, the competitive portion of the match was essentially done. The rest of the way was a chance for spectators to salute a guy who always wore his emotions on his sleeve while finishing nine consecutive seasons ranked in the top 10.

Roddick made a brief appearance at No. 1 following his only Grand Slam trophy -- and the most recent for an American man -- nine years ago. He appeared in four other major finals, losing to Roger Federer each time, and wound up with 32 tournament titles overall.

"It's been a road of a lot of ups, a lot of downs, a lot of great moments. I've appreciated your support along the way," Roddick said. "I know I certainly haven't made it easy for you at times but I really do appreciate it and love you guys with all my heart. Hopefully I'll come back to this place someday and see all of you again."

Del Potro joined the fans in standing to applaud. He moved on to a quarterfinal against defending champion Novak Djokovic, who advanced when his opponent, No. 18 Stanislas Wawrinka, stopped because of illness and fatigue while trailing 6-4, 6-1, 3-1.

Olympic champion Andy Murray became the first man to reach the semifinals, coming all the way back after being one point from facing a two-set deficit to beat No. 12 Marin Cilic 3-6, 7-6 (4), 6-2, 6-0.

Four-time major champion Maria Sharapova also turned things around to win her quarterfinal Wednesday, coming from behind after a rain delay for the second consecutive match and defeating 2007 Wimbledon runner-up Marion Bartoli 3-6, 6-3, 6-4.

Sharapova was down 4-0 on Tuesday when play was stopped. But she wound up improving to 12-0 in three-set matches this year.

"It's a great statistic. It shows that I enjoy the battle no matter what the score is," said Sharapova, who will face top-seeded Victoria Azarenka in the semifinals. "The third set, it's the last set out there, and there's no reason why you shouldn't put everything out there."

Serena Williams faced no such trouble in her quarterfinal Wednesday night.

Williams, who has won three of her 14 Grand Slam titles at the U.S. Open, hit 12 aces while defeating 2008 French Open champion Ana Ivanovic 6-1, 6-3.

Williams' semifinal opponent will be 10th-seeded Sara Errani of Italy, who eliminated her good friend and doubles partner, No. 20 Roberta Vinci, in straight sets.

The story of the day, though, was Roddick's departure -- from the tournament and from tennis -- and Williams watched his loss to del Potro.